Although muscle fatigue and weakness are often presenting symptoms in untreated human essential hypertension, they have never been systematically investigate to determine their relationship to high arterial pressure. In spontaneously hypertensive rats (SHR) however, we have described a decrease in both fatigue resistance and contractile force generation in fast and slow muscles of the hindlimb, compared to WKY normotensive controls. These functional deficits may be partially related to inherent changes in hormonal receptors or membrane transport processes in the fibers; they could also be due to a redifferentiation of slow-twitch oxidative fibers into fast-twitch glycolytic ones with associated decreases in the vasculature, as reported in some human hypertensives; or to decreased capillary blood flow, due to rarification of the terminal vascular bed, as reported in SHR cremaster muscle. We have studied anatomical distributions of muscle fiber types nad capillaries and found them to be normal in SHR; thus, this proposal will focus on changes in capillary perfusion with hypertension. The working hypothesis is that there is functional rarification of the arterioles and/or generate force. To test this hypothesis overall blood flow to muscles will be determined by infusion of radioactive microspheres; and then perfusion of arterioles (<30 um diameter) and capillaries in spinotrapezius (largely oxidative) and gracilis (largely glycolytic) will be assessed by fluorescence videomicroscopy. Fluorescently-labelled erythrocytes (XRITC) and plasma (FITC) will be infused to determine: red cell flux and velocity, capillary filling times, capillary network geometry (flow path lengths) at rest and during exercise hyperemia, in SHR and WKY, as well as renovascular hypertensive WKY and sham-operated controls. The same parameters will be studied after antihypertensive therapy with Captopril and Nifedipine and endurance exercise training to determine whether they affect capillary perfusion or the ability to generate force. Fatigue resistance and contractile force generation will also be studied in renovascular hypertensive rat hindlimbs to determine whether the defect in force generation is genetic in SHR, or related to the presence of a high arterial pressure. These experiments should clarify the relation between arterial pressure, capillary perfusion and muscle performance in hypertension.
